The present invention generally relates to implantable stimulator systems, and more particularly relates to an implantable stimulator system utilizing one or more implantable microstimulators as a therapy for erectile dysfunction.
Recent estimates suggest that the number of U.S. men with erectile dysfunction may be near 10 to 20 million, and inclusion of individuals with partial erectile dysfunction increases the estimate to about 30 million. The male erectile response is initiated by the action of neurons, or nerve cells (i.e., neuronal action), and maintained by a complex interplay between events involving blood vessels (i.e., vascular events) and events involving the nervous system (i.e., neurological events).
The part of the nervous system that regulates involuntary action (e.g., the intestines, heart, glands) is called the autonomic nervous system. The autonomic nervous system is divided into two mutually antagonistic, physiologically and anatomically distinct systems: the sympathetic nervous system and the parasympathetic nervous system. The sympathetic nervous system originates in the thoracic and lumbar regions of the spinal cord, and in general, opposes the physiological affects of the parasympathetic nervous system. For instance, the sympathetic nervous system will tend to reduce digestive secretions or speed up the heart, usually when an individual is in an active state. The parasympathetic nervous system originates in the brain stem and the lower part of the spinal cord, and, in general, opposes the physiological effects of the sympathetic nervous system. Thus, the parasympathetic nervous system will tend to stimulate digestive secretions or slow the heart usually when an individual is in a relaxed state.
It is parasympathetic neuronal action that initiates the male erectile response. Specifically, this parasympathetic input originates from the nerve plexus (i.e., a structure in the form of a network) called the pelvic splanchnic nerve plexus. The pelvic splanchnic nerve plexus is comprised of branches from the second, third, and fourth sacral nerves (from the lower part of the spinal cord) that intertwine with the inferior hypogastric plexus, which is a network of nerves in the pelvis. The cavernous nerves (designated greater and lesser) are derived from the pelvic splanchnic nerves, and supply parasympathetic fibers to the corpora cavernosum and corpus spongiosum, the erectile tissue in the penis containing large interspaces capable of being distended with blood.
This activity allows erection by relaxation of smooth muscle (i.e., muscle found in the walls of internal organs, blood vessels, hair follicles, etc. that contracts without voluntary control) and dilation of the helicine arteries, which are coiled arteries found in the erectile tissue of the penis. The dilation of the arteries causes greatly increased blood flow through the erectile tissue, which leads to expansion of the three cylinders of erectile tissue in the penis (i.e., the corpora cavernosum and the corpus spongiosum). As the corpora cavernosum and the corpus spongiosum expand, the venous structures draining the penis are compressed against the fascia surrounding each of the erectile tissues (i.e., the tunica albuginea of the corpora cavernosum and the tunica albuginea of the corpus spongiosum). Thus, the outflow of blood is restricted, and the internal pressure increases. This vein-obstruction process is referred to as the corporal veno-occlusive mechanism.
Conversely, constriction of the smooth muscle and helicine arteries induced by sympathetic innervation (i.e., stimulation by nerves) from the hypogastric nerves, for example, from certain nerves of the inferior hypogastric plexus, may make the penis flaccid.
Erectile dysfunction has a number of causes, both physiological and psychological, and in many patients the disorder may be multifactorial. The causes include several that are essentially neurologic in origin. Damage to the pathways used by the autonomic nervous system to innervate the penis may interrupt xe2x80x9cpsychogenicxe2x80x9d erection initiated by the central nervous system. Psychogenic erection has a mental or emotional origin, rather than a physical basis. Lesions (e.g., injury, infection, or disease) of the somatic nervous pathways (i.e., any of the nerves associated with sensation or motion) may impair reflexogenic erections (i.e., involuntary, instinctive physiological response to a stimulus) and may interrupt tactile sensation needed to maintain psychogenic erections. Spinal cord lesions may produce varying degrees of erectile failure depending on the location and severity of the lesions.
Not only lesions affect erectile ability; disorders leading to peripheral neuropathy may also impair neuronal innervation of the penis. Peripheral neuropathy is a disorder or abnormality of the part of the nervous system constituting the nerves outside the central nervous system and including the cranial nerves, the spinal nerves, and the sympathetic and parasympathetic nervous systems. Peripheral neuropathy may also impair neuronal innervation of the sensory afferentsxe2x80x94the nerves that conduct impulses from the periphery of the body to the brain or spinal cord, transmitting impulses from sense organs to nerve centers. Peripheral neuropathy is a potential sequela of a number of diseases, e.g., diabetes mellitus.
The endocrine system (glands such as the thyroid, adrenal, or pituitary, having hormonal secretions that pass directly into the bloodstream), particularly the production of androgens (steroid hormones, such as testosterone or androsterone, that control the development and maintenance of masculine characteristics), appears to play a role in regulating sexual interest, and may also play a role in erectile function.
In men of all ages, erectile failure may diminish willingness to initiate sexual relationships because of fear of inadequate sexual performance or rejection. Because males, especially older males, are particularly sensitive to the social support of intimate relationships, withdrawal from these relationships because of such fears may have a negative effect on their overall health.
Some forms of erectile dysfunction are currently treated with medication, with varying degrees of success. For instance, the well-publicized oral medication VIAGRA(copyright) (active ingredient sildenafil citrate) requires an hour to exert its full effects, and it may have significant side effects such as abnormal vision, flushing, headache, and diarrhea.
Intracavernosal injection therapy, in which a patient injects vasodilator substances (e.g., papaverine) into the corpora of the penis, suffers a high rate of patient dropout, as does the therapeutic application of vacuum constriction devices. Several forms of penile prostheses are available, including semirigid, malleable, and inflatable, but these have significant problems with mechanical failure, infection, and device erosion.
Various stimulation devices have been proposed for treating erectile dysfunction. Some devices stimulate through the skin, such as intrarectal stimulation devices. Other devices require significant surgical procedures for placement of electrodes, leads, and processing units. These devices may also require an external apparatus that needs to be strapped or otherwise affixed to the skin. While several patents exist regarding stimulators for treatment of erectile dysfunction, the inventors know of no chronic, fully implantable neurostimulator device that is commercially available.
The invention disclosed and claimed herein provides means for chronically stimulating nerves derived from the pelvic splanchnic plexus, such as the cavernous nerves, with a miniature implantable neurostimulator that can be implanted with a minimal surgical procedure. Prior research suggests that stimulation of the cavernous nerve(s) may be an effective therapy for erectile dysfunction.
The cavernous nerves are relatively accessible as they run subcutaneously at the base of the dorsal penis. To treat erectile dysfunction, a miniature implantable neurostimulator, such as a Bionic Neuron (also referred to as a BION(trademark) microstimulator) may be implanted adjacent to the cavernous nerves via a minimal surgical procedure (e.g., injection or small incision). A microstimulator may be implanted via injection and/or via endoscopic means. A more complicated surgical procedure may be required for sufficient access to a nerve or portion of a nerve (e.g., nerve fibers surrounded by scar tissue) or for purposes of fixing the neurostimulator in place.
A single microstimulator may be implanted, or two or more microstimulators may be implanted to achieve greater stimulation of the nerve fibers (e.g., all branches of the greater and lesser cavernous nerves). Alternatively, a microstimulator(s) may be implanted adjacent to parasympathetic targets deeper in the patient""s body, such as the proximal cavernous nerves, the prostatic plexus, the pelvic splanchnic nerves, or the second, third, and/or fourth sacral nerves (i.e., S2, S3, S4). In order to inhibit sympathetic input that, e.g., retards erection, a microstimulator(s) may also/instead be implanted adjacent to the hypogastric nerve, certain nerves of the inferior hypogastric plexus or its branches, or the sympathetic ganglia from which the hypogastric nerve is derived.
Stimulation and control parameters of the implanted microstimulator are preferably adjusted to levels that are safe and efficacious with minimal discomfort. Different stimulation parameters have different effects on neural tissue, and parameters may be chosen to target specific neural populations and to exclude others. For example, relatively low frequency neurostimulation (i.e., less than about 50-100 Hz) may have an excitatory effect on surrounding neural tissue, leading to increased neural activity, whereas relatively high frequency neurostimulation (i.e., greater than about 50-100 Hz) may have an inhibitory effect, leading to decreased neural activity.
According to one embodiment of the invention, the stimulation can increase excitement of the parasympathetic input to, e.g., the penis; low-frequency electrical stimulation of parasympathetic fibers is likely to produce such excitement. According to another embodiment of the invention, the stimulation can decrease excitement of the sympathetic input to, e.g., the penis; high-frequency electrical stimulation of sympathetic fibers is likely to produce such inhibition.
The neurostimulator also includes means of stimulating nerve fibers either intermittently or continuously. Specific stimulation parameters may provide therapeutic advantages for various forms of erectile or other sexual dysfunction. Additional uses include the applications to emission (discharge of semen), ejaculation (ejection of semen in orgasm), and female sexual dysfunction.
It should be noted that the present invention is not directed to the xe2x80x9cmicrostimulatorxe2x80x9d, per se, which is the subject of other patents and patent applications, but is rather directed to methods of using the microstimulator, or a group of microstimulators, to treat erectile and other sexual dysfunction. However, the microstimulator used with the present invention preferably possesses one or more of the following properties:
at least two electrodes for applying stimulating current to surrounding tissue;
electronic and/or mechanical components encapsulated in a hermetic package made from biocompatible material(s);
an electrical coil inside the package that receives power and/or data by inductive or radio-frequency (RF) coupling to a transmitting coil placed outside the body, avoiding the need for electrical leads to connect devices to a central implanted or external controller;
means for receiving and/or transmitting signals via telemetry;
means for receiving and/or storing electrical power within the microstimulator; and
a form factor making the microstimulator implantable via a minimal surgical procedure.
The power source of the microstimulator is preferably realized using one or more of the following options:
(1) an external power source coupled to the microstimulator via an RF link;
(2) a self-contained power source made using any means of generation and/or storage of energy, e.g., a primary battery, a replenishable or rechargeable battery, a capacitor, a supercapacitor; and/or
(3) if the self-contained power source is replenishable or rechargeable, means of replenishing or recharging the power source, e.g., an RF link, an optical link, or other energy-coupling link.
A microstimulator may operate independently, or in a coordinated manner with other implanted devices, or with external devices. In addition, a microstimulator may incorporate means for sensing erectile or other sexual dysfunction, which it may then use to control stimulation parameters in a closed loop manner. According to one embodiment of the invention, the sensing and stimulating means are incorporated into a single microstimulator. According to another embodiment of the invention, a sensing means communicates sensed information to at least one microstimulator with stimulating means.
Thus, the present invention provides a therapy for erectile and other sexual dysfunction that utilizes one or more miniature neurostimulators and is minimally invasive. The simple implant procedure results in reduced surgical time and possible error, with associated advantages in terms of reduced expense and opportunity for infection or other complications. Other advantages, inter alia, of the present invention the system""s monitoring and programming capabilities, the power source, storage, and transfer mechanisms, the activation of the device by the patient or clinician, the system""s open and closed-loop capabilities and closed-loop capabilities coupled with sensing a need for and/or response to treatment, coordinated use of one or more stimulators, and the small size of the stimulator.